Human T cell clones specific for hnRNP A2 autoantigen assist in autoantibody production

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Arthritis Rheum. 2004 Jul;50(7):2216-22.

Human T cell clones specific for heterogeneous nuclear ribonucleoprotein

A2 autoantigen from connective tissue disease patients assist in

autoantibody production.

Greidinger EL, Gazitt T, s KF, Hoffman RW.

University of Miami, and the Veterans Affairs Medical Center, Miami,

Florida, USA.

OBJECTIVE: To identify and characterize human T cells reactive with

heterogeneous nuclear RNP A2 (hnRNP A2) antigen, and to determine the

ability of hnRNP-reactive T cells to assist in the production of human

autoantibodies. METHODS: T cells from patients with high serum levels of

anti-hnRNP IgG autoantibody were stimulated with an hnRNP recombinant

fusion protein, and the cells were cloned by limiting dilution. The

surface phenotype and cytokine profiles of the T cells were examined by

flow cytometry and enzyme-linked immunosorbent assay (ELISA),

respectively. T cell clones were cultured with highly purified

autologous B cells, and the ability of T cells to enhance autoantibody

production under a variety of conditions was measured by ELISA. RESULTS:

Human T cells reactive with hnRNP antigen were cloned from 2 patients

with systemic lupus erythematosus (SLE) and 1 patient with mixed

connective tissue disease (MCTD). The T cells were CD4+ and had a

Th1-like functional phenotype. In coculture in vitro with autologous B

cells, T cell clones augmented anti-hnRNP autoantibody production and

did so without the need for direct T cell-B cell contact.

CONCLUSION: This study provides direct evidence for a role of

anti-hnRNP-reactive T cells in autoantibody production in SLE and MCTD.

These findings support the notion that hnRNP-reactive T cells play a

role in the pathogenesis of these diseases.

PMID: 15248220

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